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1.
Aust J Rural Health ; 32(2): 249-262, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38646861

RESUMEN

INTROUDCTION: There is increased risk of skin cancer in patients with gloermular disease or those with renal transplant. OBJECTIVES: To compare the risk of skin cancer between kidney recipients (KTRs) and patients with glomerular disease (GD). DESIGN: The cohort comprised patients with KTRs (n = 61) and GD (n = 51) in Central and Central West Queensland, Australia. A quantitative cohort study was undertaken to study the risk of skin cancer in rural communities between two subgroups of patients with kidney diseases in relationship to immunosuppression. Statistical analyses of the differences in incidence of skin cancers between the two groups were done by chi-square test, Fisher's exact test, independent t-test and McNemar's test. FINDINGS: KTRs with non-melanoma skin carcinoma (NMSC) increased significantly after treatment with immunosuppressants (pre-transplantation, n = 11 [18.0%], post-transplantation, n = 28 [45.9%]; p < 0.001). There were no differences in number of patients with NMSC observed in the GD group (pre-diagnosis, n = 6 [11.8%], post-diagnosis, n = 7 [13.7%]; p = 1.000). Compared to the risks at 1 year post-immunosuppressants, the incidence of NMSC of KTRs increased significantly at 3 years (20.3% vs. 35.4%, p < 0.001) and 5 years (20.3% vs. 62.2%, p < 0.001) post-immunosuppressants, whereas the increased incidence of NMSC was observed only at 5 years (2.1% vs. 11.8%, p = 0.012) in the GD cohort. The mean cumulative number of NMSC in KTRs increased significantly at 3 years (p = 0.011), and 5 years (p = 0.001) post-immunosuppressants, compared to the risks at 1 year post-immunosuppressants, however, no differences were noted in the GD cohort. DISCUSSION: Immunosuppressants increased the risk of NMSC in KTRs. The increased risk is likely dependent on the intensity and duration of immunosuppressants. CONCLUSION: In patients with a high risk of NMSC, reducing skin cancer risk should be considered in conjunction with the optimisation of treatment.


Asunto(s)
Trasplante de Riñón , Neoplasias Cutáneas , Humanos , Queensland/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/epidemiología , Adulto , Población Rural/estadística & datos numéricos , Anciano , Estudios de Cohortes , Incidencia , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Factores de Riesgo , Receptores de Trasplantes/estadística & datos numéricos
2.
Oral Dis ; 29(3): 892-901, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-34653303

RESUMEN

Oral and maxillofacial tumors (OMTs), such as oral squamous cell carcinoma (SCC), pleomorphic adenoma, and ameloblastoma, are common head and neck tumors. Lipopolysaccharide-binding protein (LBP) is a type I acute reactive protein, which participates in body inflammatory response modulation through lipopolysaccharide (LPS)-induced signaling pathway by targeting macrophages (expressing cluster of differentiation 204 [CD204]). Although it is well established that LBP is associated with the development of multiple types of cancer, little is known about the role of LBP in OMTs. This study aims to explore the expression of LBP in OMTs. Here, immunohistochemical (IHC) double staining of LBP and CD204 and enzyme-linked immunosorbent assay (ELISA) were conducted to explore the LBP expression in OMTs. The findings demonstrated that the LBP expression in OMTs was significantly elevated (p < 0.001). In addition, the LBP expression was associated with the clinical stage (p < 0.001), T classification (p < 0.001), and lymph node metastasis (p < 0.001, except ELISA) but independent of histological grade of SCC, gender, and age in patients with SCC. The optional cutoff of the LBP serum level is 0.721 µg/ml. To conclude, LBP contributes to the development of OMTs and could be a biomarker in the screening and predicting metastasis in patients with OMTs.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Biomarcadores
3.
Oral Dis ; 29(4): 1464-1479, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-34990052

RESUMEN

OBJECTIVE: Studies have shown that cancer progression of head and neck squamous cell carcinoma (HNSCC) is related with metabolic alterations. The aim of this study is to identify the clinical roles of metabolic alterations in HNSCC. MATERIALS AND METHODS: Metabolism-related genes associated with HNSCC were searched in public databases. A predictive and efficacious LASSO model was fabricated to optimize the diagnosis that was based on these genes. Meantime, ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to compare patients with HNSCC (n = 73) with healthy controls (n = 51) for serum metabolites. Potential biomarkers and alterations in serum metabolites were analysed and evaluated using t test analysis, principal component analysis and orthogonal partial least square-discrimination analysis. RESULTS: Overall, 21 differential metabolites were probed in serum, of which eight metabolites had potential for clinical uses. Transcriptome analysis showed that four genes in the constructed LASSO model were found to be associated with seven differential metabolites. Metabolic pathway analysis by MetaboAnalyst showed that the biomarkers that were related with HNSCC were closely related to four metabolism pathways (p < 0.05). CONCLUSION: To conclude, future research on HNSCC should be directed towards multi-omics to provide treatment, intervention or diagnosis of the disease.


Asunto(s)
Neoplasias de Cabeza y Cuello , Transcriptoma , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Metabolómica/métodos , Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética
4.
Intern Med J ; 53(11): 2042-2049, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36710434

RESUMEN

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.


Asunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Trasplante de Riñón , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Femenino , Persona de Mediana Edad , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Estrés Financiero , Australia/epidemiología , Factores de Riesgo , Programas Nacionales de Salud , Neoplasias Cutáneas/epidemiología , Receptores de Trasplantes
5.
Int J Mol Sci ; 24(5)2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36902476

RESUMEN

Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of p53, APC, KRAS, c-Myc, and immunotherapeutic target molecules PD-L1, CTLA-4, and CD47 in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages (p = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, p = 0.019), while being weakly correlated with tumour size (p = 0.051). Patients with lower numbers of CTCs had higher expression of KRAS. Higher KRAS expression in CTCs was negatively correlated with tumour perforation (p = 0.029), lymph node status (p = 0.037), distant metastasis (p = 0.046) and overall staging (p = 0.004). CTLA-4 was highly expressed in both CTCs and PBMCs. In addition, CTLA-4 expression was positively correlated with KRAS (r = 0.6878, p = 0.002) in the enriched CTC fraction. Dysregulation of KRAS in CTCs might evade the immune system by altering the expression of CTLA-4, providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.


Asunto(s)
Neoplasias Colorrectales , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Antígeno CTLA-4/metabolismo , Leucocitos Mononucleares/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/patología , Genes Reguladores , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Microambiente Tumoral
7.
Curr Psychol ; : 1-15, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-37359655

RESUMEN

The present research reports the findings of three studies, with objectives to demonstrate the impacts of health-promoting behaviors on psychological well-being as well as the mediating roles of sense of control (SOC) and perceived severity of COVID-19 in these relationships. Study 1 was a cross-sectional survey conducted in 473 middle-aged and older Chinese adults before the COVID-19 pandemic to assess their health-promoting behaviors, personal mastery and perceived constraints, life satisfaction, and depressive symptoms. Study 2 was conducted during the second wave of the COVID-19 outbreak in Hong Kong (between March to April 2020), in which 292 participants from Study 1 were successfully contacted to report their emotional responses to the pandemic. Using a different sample, Study 3 was a longitudinal study that measured 495 participants' health-promoting behaviors, personal mastery and perceived constraints at baseline, and their perceived severity and mental health outcomes during the outbreak of omicron cases in Hong Kong (i.e., the fifth wave of the COVID-19 outbreak) in March 2022. All three studies demonstrate that the beneficial effects of health behaviors can be extended to psychological well-being and reveal possible underlying mechanisms through enhancing one's SOC and lowering perceived severity of the COVID-19 outbreak. These results provide important insights to future health promotion programs for improving psychological resources and psychological well-being of middle-aged and older adults in face of disease-related threats.

8.
Br J Cancer ; 127(7): 1304-1311, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35842545

RESUMEN

BACKGROUND: The clinical utility of comprehensive genomic profiling (CGP) for guiding treatment has gradually become the standard-of-care procedure for colorectal carcinoma (CRC). Here, we comprehensively assess emerging targeted therapy biomarkers using CGP in primary CRC. METHODS: A total of 575 primary CRCs were sequenced by ACTOnco® assay for genomic alterations, tumour mutational burden (TMB), and microsatellite instability (MSI). RESULTS: Eighteen percent of patients were detected as MSI-High (MSI-H), and the remaining cases were classified as microsatellite stable (MSS). Driver mutation prevalence in MSS CRCs were APC (74%), TP53 (67%), KRAS (47%), PIK3CA (21%) and BRAF (13%). The median TMBs for MSI-H and MSS patients were 37.8 mutations per mega base (mut/Mb) and 3.9 mut/Mb, respectively. Forty-seven percent of MSI-H CRC harboured at least one loss-of-function mutations in genes that may hamper immune checkpoint blockade. Among MSS RAS/RAF wild-type CRCs, 59% had at least one actionable mutation that may compromise the efficacy of anti-EGFR therapy. For late-stage CRC, 51% of patients are eligible for standard care actionability and the remaining 49% could be enrolled in clinical trials with investigational drugs. CONCLUSIONS: This study highlights the essential role of CGP for identifying rational targeted therapy options in CRC.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas B-raf , Humanos , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Drogas en Investigación , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Inhibidores de Puntos de Control Inmunológico , Inestabilidad de Microsatélites , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética
9.
J Oral Pathol Med ; 51(3): 249-255, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34586677

RESUMEN

BACKGROUND: Circulating tumour cells (CTCs) detected in patient blood samples are relevant as diagnostic and prognostic markers offering insights into tumour behaviour and guiding treatment of cancer at an individualised level. The aim of this study was to ascertain the feasibility of detecting CTCs in oral squamous cell carcinoma (OSCC) using two different methods so as to determine the optimal method for the study of this cancer. METHODS: Comparison of the numbers of CTCs, circulating tumour micro-emboli (CTMs) and circulating tumour endothelial cells (CTECs), was undertaken in forty clinical samples of oral squamous cell carcinoma (OSCC) determined by filtration (ISET® ) and in situ fluorescent immunostaining (i-FISH, Cytelligen® ) immunostaining and in situ hybridisation. RESULTS: i-FISH detected CTCs in 80% of samples compared with 40% of samples analysed by microfiltration. i-FISH detected CTCs in a further 40% of samples in which microfiltration did not detect CTCs. No CTC clusters were detected by microfiltration while i-FISH detected CTM in 12.5% of samples. i-FISH analysis detected CTECs in 20/40 samples. CONCLUSION: These results highlight significant differences in detection of CTCs, CTM and CTECs between i-FISH and microfiltration when applied to OSCC samples, suggesting that technologies capable of detecting circulating aneuploid cells more accurately detect CTCs. i-FISH also detected CTM and CTEC not detected using ISET® . With proven prognostic relevance in adenocarcinomas, accurate enumeration of CTCs, CTMs and CTECs may be a clinically useful tool in the management of OSCC and may aid in the reduction of false-negative diagnoses.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Células Neoplásicas Circulantes , Biomarcadores de Tumor , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Células Endoteliales/patología , Humanos , Neoplasias de la Boca/diagnóstico , Células Neoplásicas Circulantes/patología
10.
Int J Colorectal Dis ; 37(3): 541-551, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35152308

RESUMEN

PURPOSE: The purpose of the study is to assess the global risk of extracolonic secondary primary cancers (SPCs) in patients with colorectal cancer (CRC). METHODS: Studies of SPC in patients with CRC were included if they reported the standardised incidence ratio (SIR) for extracolonic SPCs in patients with CRC compared with the general population. Pooled summary estimates were calculated using a random-effects model. RESULTS: A total of 7,716,750 patients with CRC from 13 retrospective cohort studies that reported extracolonic SPC incidence were included. The overall risk of several SPCs was significantly higher in patients with CRC compared with the general population, including cancers of the urinary bladder (pooled SIR 1.19, 95% confidence interval (CI) 1.06-1.33; p = 0.003), female genital tract (1.88, 1.07-3.31; p = 0.03), kidney (1.50, 1.19-1.89; p = 0.0007), thorax (lung, bronchus and mediastinum) (1.16, 1.01-1.32; p = 0.03), small intestine (4.26, 2.58-7.01; p < 0.0001), stomach (1.22, 1.07-1.39; p = 0.003), and thyroid (1.40, 1.28-1.53; p < 0.0001), as well as melanoma (1.28, 1.01-1.62; p = 0.04). There was also a decreased risk of developing cancer of the gall bladder (0.75, 0.60-0.94; p = 0.01). CONCLUSION: Patients with CRC had a significantly increased risk of extracolonic SPCs compared with the general population. These findings highlight the need to develop research strategies for the management of second primary cancer in patients with CRC.


Asunto(s)
Neoplasias Colorrectales , Melanoma , Neoplasias Primarias Secundarias , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/epidemiología , Femenino , Humanos , Incidencia , Melanoma/complicaciones , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Estudios Retrospectivos , Factores de Riesgo
11.
BMC Nephrol ; 23(1): 361, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-36357857

RESUMEN

Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p < 0.001) and 6-months post-intervention (p < 0.01). Improved knowledge was retained for 6 months after education. There were changes in 2 of 8 photoprotective behaviours at 6 months. Interventional education enhanced regular self-skin examination rate (p < 0.001) as well as the frequency of full skin checks by general practitioners (GPs) (p < 0.001). Overall, RTRs had better compliance with sun-protective methods and higher skin examination rates by themselves and/ or GPs before and after the intervention of education compared to patients with GD. To conclude, an integrated skin cancer education program improved knowledge of skin cancer and skin health as well as the frequency of self-skin examination and formal skin assessments. However, improvement in patient compliance did not extend to other sun-protective practices.


Asunto(s)
Educación en Salud , Enfermedades Renales , Trasplante de Riñón , Neoplasias Cutáneas , Adulto , Humanos , Conocimientos, Actitudes y Práctica en Salud , Enfermedades Renales/etiología , Trasplante de Riñón/efectos adversos , Estudios Prospectivos , Neoplasias Cutáneas/prevención & control , Receptores de Trasplantes
12.
BMC Med Educ ; 22(1): 22, 2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-34996435

RESUMEN

BACKGROUND: Medical and pathology education has gone through an immense transformation from traditional face-to-face teaching mode to virtual mode during the COVID-19 pandemic. This study evaluated the effectiveness of online histopathology teaching in medical education during the 2020 COVID-19 pandemic in Griffith University, Australia. METHODS: Second-year medical students (n = 150) who had previously completed one year of face-to-face histopathology teaching, completed an online questionnaire rating their learning experiences before and during the COVID-19 pandemic after the completion of their histology and pathology practical sessions. The students' histopathology assessment results were then compared to the histopathology results of a prior second-year cohort to determine if the switch to online histopathology teaching had an impact on students' learning outcome. RESULTS: A thematic analysis of the qualitative comments strongly indicated that online histopathology teaching was instrumental, more comfortable to engage in and better structured compared to face-to-face teaching. Compared to the previous year's practical assessment, individual performance was not significantly different (p = 0.30) and compared to the prior cohort completing the same curriculum the mean overall mark was significantly improved from 65.36% ± 13.12% to 75.83% ± 14.84% (p < 0.05) during the COVID-19 impacted online teaching period. CONCLUSIONS: The transformation of teaching methods during the 2020 COVID-19 pandemic improved student engagement without any adverse effects on student learning outcomes in histology and pathology education.


Asunto(s)
COVID-19 , Estudiantes de Medicina , Humanos , Aprendizaje , Pandemias , SARS-CoV-2
13.
Int J Mol Sci ; 23(6)2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-35328664

RESUMEN

Secondary tumours to the thyroid gland are uncommon and often incidentally discovered on imaging. Symptomatic patients often present with a neck mass. Collision tumours of secondary tumours and primary thyroid neoplasms do occur. Ultrasound-guided fine-needle aspiration, core-needle biopsy, and surgical resection with histological and immunohistochemical analysis are employed to confirm diagnosis as well as for applying molecular studies to identify candidates for targeted therapy. Biopsy at the metastatic site can identify mutations (such as EGFR, K-Ras, VHL) and translocations (such as EML4-ALK fusion) important in planning target therapies. Patients with advanced-stage primary cancers, widespread dissemination, or unknown primary origin often have a poor prognosis. Those with isolated metastasis to the thyroid have better survival outcomes and are more likely to undergo thyroid resection. Systemic therapies, such as chemotherapy and hormonal therapy, are often used as adjuvant treatment post-operatively or in patients with disseminated disease. New targeted therapies, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, have shown success in reported cases. A tailored treatment plan based on primary tumour features, overall cancer burden, and co-morbidities is imperative. To conclude, secondary cancer to the thyroid is uncommon, and awareness of the updates on diagnosis and management is needed.


Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias de la Tiroides , Biopsia con Aguja Fina , Humanos , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Ultrasonografía
14.
Int J Cancer ; 148(5): 1040-1050, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-32674220

RESUMEN

The WHO Classification of Tumours provides the international standards for the classification and diagnosis of tumours. It enables direct comparisons to be made between different countries. In the new fifth edition, the series has gone digital with the launch of a website as well as a series of books, known widely as the WHO Blue Books. The first volume to be produced is on the classification of Digestive System tumours, replacing the successful 2010 version. It has been rewritten and updated accordingly. This article summarises the major diagnostic innovations that have occurred over the last decade and that have now been incorporated in the classification. As an example, it incorporates the recently proposed classification of neuroendocrine tumours, based on the recognition that neuroendocrine tumours and carcinomas differ substantially in the genetic abnormalities that drive their growth, findings relevant to treatment selection and outcome prediction. Several themes have emerged during the production process. One is the importance of the progression from hyperplasia to dysplasia to carcinoma in the evolution of the malignant process. Advances in imaging techniques and endoscopy have resulted in enhanced access to precancerous lesions in the gastrointestinal and biliary tract, necessitating both changes in classification schema and clinical practice. Diagnosis of tumours is no longer the sole purview of pathologists, and some patients now receive treatment before tissue is obtained, based on clinical, radiological and liquid biopsy results. This makes the classification relevant to many disciplines involved in the care of patients with tumours of the digestive system.


Asunto(s)
Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias del Sistema Digestivo/clasificación , Neoplasias Gastrointestinales/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico
15.
Exp Mol Pathol ; 120: 104642, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33905708

RESUMEN

PURPOSE: Heme is a crucial compound for cell survival but is also equipped with the potential to be toxic and carcinogenic to cells. However, with the recent advancement of knowledge regarding ferroptosis, the iron mediated cell death, heme can be postulated to induce tumour suppression through ferroptosis. This review summarizes the literature on the carcinogenic and anticarcinogenic properties of heme with specific emphasis on the alterations observed on heme synthesis, metabolism and transport in tumour cells. METHODS: Literature search was performed in PubMed data base using the MeSH terms 'heme iron or heme', 'cancer or carcinogenesis' and 'tumour suppression' or 'anticarcinogenic properties. Out of 189 results, 166 were relevant to the current review. RESULTS: Heme supports carcinogenesis via modulation of immune cell function, promoting inflammation and gut dysbiosis, impeding tumour suppressive potential of P53 gene, promoting cellular cytotoxicity and reactive oxygen species generation and modulating Nfr2 /HO-1 axis. The carcinogenic and anticarcinogenic properties of heme are both dose and oxygen concentration dependant. At low doses, heme is harmless and even helpful in maintaining the much-needed redox balance within the cell. However, when heme exceeds physiological concentrations, it could initiate and propagate carcinogenesis, due to its ability to produce reactive oxygen species (ROS). The same phenomenon of heme mediated ROS generation could be manipulated to initiate tumour suppression via ferroptosis, but the therapeutic doses are yet to be determined. CONCLUSION: Heme iron possesses powerful carcinogenic and anticarcinogenic properties which are dosage and oxygen availability dependant.


Asunto(s)
Carcinogénesis/patología , Hemo/metabolismo , Hierro/metabolismo , Neoplasias/patología , Neoplasias/prevención & control , Carcinogénesis/genética , Carcinogénesis/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Humanos , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
16.
Curr Oncol Rep ; 23(3): 31, 2021 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-33582932

RESUMEN

PURPOSE OF REVIEW: Anaplastic thyroid carcinoma is a type of thyroid carcinoma with the most aggressive biological behaviour amongst thyroid cancer. Here, we review the current genomic and the impacts of advances in therapies to improve the management of patients with the cancer. RECENT FINDINGS: Common mutations being identified in anaplastic thyroid carcinoma are p53 and TERT promoter mutations. Other common mutated genes included BRAF, RAS, EIF1AX, PIK3CA, PTEN and AKT1, SWI/SNF, ALK and CDKN2A. Changes in expression of different microRNAs are also involved in the pathogenesis of anaplastic thyroid carcinoma. Curative resection combined with radiotherapy and combination chemotherapies (such as anthracyclines, platins and taxanes) has been shown to have effects in the treatment of some patients with anaplastic thyroid carcinoma. Newer molecular targeted therapies in clinical trials target mostly the cell membrane kinase and downstream proteins. These include targeting the EGFR, FGFR, VEGFR, c-kit, PDGFR and RET on the cell membrane as well as VEGF itself and the downstream targets such as BRAF, MEK and mTOR. Immunotherapy is also being tested in the cancer. Updated knowledge of genomic as well as clinical trials on novel therapies is needed to improve the management of the patients with this aggressive cancer.


Asunto(s)
Terapia Molecular Dirigida/métodos , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/terapia , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Genómica , Humanos , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/patología
17.
Nephrology (Carlton) ; 26(11): 907-919, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34240786

RESUMEN

With an increasing number of renal transplant recipients (RTRs) and improving patient survival, a higher incidence of non-melanoma skin cancer (NMSC) has been observed. NMSC in RTRs are often more numerous and biologically more aggressive than the general population, thus contributing towards an increase in morbidity and to a lesser degree, mortality. The resultant cumulative health and financial burden is a recognized concern. Proposed strategies in mitigating risks of developing NMSC and early therapeutic options thereof include tailored modification of immunosuppressants in conjunction with sun protection in all transplant patients. This review highlights the clinical and financial burden of transplant-associated skin cancers, carcinogenic mechanisms in association with immunosuppression, importance of skin cancer awareness campaign and integrated transplant skin clinic, and the potential role of chemoprotective agents. A scheme is proposed for primary and secondary prevention of NMSC based on the available evidence.


Asunto(s)
Trasplante de Riñón/efectos adversos , Neoplasias Cutáneas/prevención & control , Animales , Anticarcinógenos/uso terapéutico , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Incidencia , Pronóstico , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad
18.
Nephrology (Carlton) ; 26(4): 294-302, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34308553

RESUMEN

BACKGROUND: There is no previous study that compare skin cancer awareness and photoprotective behaviours between renal transplant recipients (RTR) and patients with glomerular disease (GD). OBJECTIVES/METHODS: Sixty-one RTR and 51 patients with GD were given a self-reported questionnaire to evaluate skin cancer awareness and photoprotective behaviours in this cross-sectional study. The former group received a formal education on skin cancer and the latter an informal session prior to immunosuppressant use. RESULTS: Ninety-three percent (n = 57) of RTRs and 88% (n = 45) of patients with GD responded to the survey. Majority of participants from both groups were aware that ultraviolet radiation could play a role in the occurrence of skin cancers and the awareness increased in participants with higher education (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.15-1.95, P = .003). Ninety-eight percent vs 71% were aware that immunosuppressants can increase the risk of developing cancer (P < .001) and higher awareness was noted in younger participants (OR = 0.92, 95% CI = 0.87-0.97, P = .003). Suboptimal photoprotective behaviours (sun avoidance, sunscreen usage and sun-protective clothing) were noted in both cohorts and slightly lower sun protection rates were reported in RTR when compared with patients having GD. The level of sun protective measures in RTR based on high, moderate and minimal use of photoprotective measures were 21%, 46% and 33%, respectively. In terms of patients with GD, the latter practices were 13%, 50% and 37%, respectively (P = .560). Higher educational status was significantly associated with better sunscreen usage in RTR (P = .017) whereas this finding was not observed in patients with GD. CONCLUSION: Patients with GD and RTR should have formal education on the risks of skin cancers before starting immunosuppressants. Follow-up education and surveillance is required to improve skin protective practices in these patients.


Asunto(s)
Glomerulonefritis/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Inmunosupresores/efectos adversos , Trasplante de Riñón , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Receptores de Trasplantes , Rayos Ultravioleta/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Glomerulonefritis/diagnóstico , Glomerulonefritis/inmunología , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/etiología , Neoplasias Inducidas por Radiación/inmunología , Educación del Paciente como Asunto , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/inmunología , Adulto Joven
19.
BMC Geriatr ; 21(1): 128, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33596829

RESUMEN

BACKGROUND: Middle-aged and older adults are more vulnerable to hospitalization and mortality if they are infected with the COVID-19 virus. The present study investigates the longitudinal effects of subjective successful aging on middle-aged and older adults' emotional and coping responses to the COVID-19 pandemic, and explores an underlying mechanism through perceived time limitation during the pandemic. METHODS: A sample of 311 Hong Kong Chinese middle-aged and older adults (Mage = 64.58, SD = 10.14, Range = 45-90 years) were recruited from an Adult Development and Aging Project and participated in a questionnaire study via an online platform or phone interview. Their levels of subjective successful aging, perceived time limitation, and emotional and coping responses to the pandemic were measured. RESULTS: The respondents who perceived themselves as more successful in aging process reported more positive and fewer negative emotions compared with their counterparts with lower levels of subjective successful aging. The mediation analysis showed that perceived time limitation could partially account for the effects of subjective successful aging on emotional and coping responses. CONCLUSIONS: Findings of this study unveil the beneficial effects of subjective views of successful aging on emotional and coping responses to the pandemic through alleviating their perception of time limitation.


Asunto(s)
COVID-19 , Pandemias , Adaptación Psicológica , Anciano , Anciano de 80 o más Años , Envejecimiento , Emociones , Hong Kong/epidemiología , Humanos , Persona de Mediana Edad , SARS-CoV-2
20.
Echocardiography ; 38(9): 1503-1513, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34355811

RESUMEN

BACKGROUND: Left atrial analysis is employed in diastolic assessment with left atrial volume index (LAVI) incorporated in the 2016 ASE/EACVI diastology guideline algorithm. LAVI has sub-optimal correlation with invasive left ventricular filling pressure (LVFP) and incorporation of left atrial reservoir strain (LASr) may improve diastolic assessment. METHODS: A cross-sectional prospective study of 139 patients was undertaken with all patients undergoing transthoracic echocardiography immediately prior to cardiac catheterization with invasive evaluation of LVFP. LASr by speckle tracking echocardiography and conventional echocardiographic parameters were assessed in relation to invasive LVFP. Modification of the 2016 guideline algorithm was performed with incorporation of LASr in place of LAVI (LASr ≤23% indicating elevated LVFP). Accuracy of the modified and conventional algorithm were assessed for predicting invasive LVFP. RESULTS: The mean age was 63±12 years with 27% female. LASr demonstrated superior correlation and receiver operator characteristic for predicting LVFP than LAVI (LASr: r -.46 (p < 0.01), AUC: .82 vs LAVI: r .19 (p 0.02), AUC: .66). LASr of ≤23% was the optimal cut-off for discriminating elevated LVFP (sensitivity 80%, specificity 77%). Modification of the 2016 algorithm with incorporation of LASr in place of LAVI reclassified 12% of the patient cohort and improved concordance of echocardiographic and invasive LVFP assessment (modified algorithm κ .47 vs 2016 algorithm κ: .33). No patients were incorrectly reclassified by modified algorithm assessment. CONCLUSIONS: LASr better predicts invasive LVFP than LAVI. Modification of the 2016 guideline algorithm with incorporation of LASr in place of LAVI improves accuracy of echocardiographic assessment of LVFP.


Asunto(s)
Disfunción Ventricular Izquierda , Anciano , Estudios Transversales , Femenino , Atrios Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico , Función Ventricular Izquierda
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